How To Assess Severity and Prognosis Gregory Tino, M.D. Chief, Department of Medicine Penn Presbyterian Medical Center Associate Professor of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia, PA
Disclosures Research grant support: Bronchiectasis Research Registry/COPD Foundation Advisory Board: Bayer Grifols Aradigm
Assessing Severity and Prognosis Clinical course and natural history of bronchiectasis are variable Ability to accurately assess severity and prognosis has been an unmet need.. but we ve made significant progress
77 y.o. African-American man: Followed at Penn since 1966 Pneumonia at 18 months of age Diagnosed with bronchiectasis in Alabama at age 12 after presenting with cough of two years duration with ½ cup purulent sputum production Tuberculosis excluded
Clinical Course Left pneumonectomy recommended, but declined by his parents Did well as teenager and adult - fathered two children, retired after career as a parole officer Managed for many years with rotating antibiotics, including ciprofloxacin, + chest physiotherapy
PFT FEV 1 : 1.65L (72% pred) 2.17L FVC: 2.10 L (68% pred) 2.70L FEV 1 / FVC ratio: 78% 80% TLC: 75% predicted RV: 110% predicted D L CO: 60% predicted 2014 2004
Clinical Course Has quinolone-resistant Pseudomonas aeruginosa infection + Pulmonary MAC infection (macrolide-sensitive, for which he s declined antimicrobials) 2-3 acute infectious exacerbations per year requiring IV antibiotics Daily sputum production - 40ml/day Perceives QOL as declining
How would you assess the severity of this patient s bronchiectasis?
Bronchiectasis: Clinical Impact Has adverse impact on quality of life Factors influencing QOL Dyspnea FEV 1 Sputum volume Pseudomonas aeruginosa infection Wilson et al. Eur Respir J 1997;10:1754-60. Martinez-Garcia et al. Chest 2005;128:739-745.
Bacterial load is a significant predictor of recurrent exacerbations and an independent predictor of hospitalization ** * * * * Antibiotic therapy reduces bacterial load and markers of inflammation. Bacterial load cfu/ml Bacterial load cfu/ml 0 10 5 10 6 10 7 10 8 Chalmers, et al. AJRCCM, 2012.
Mortality in Bronchiectasis 91 patients in the UK followed over 13 years starting in 1994; 56% had idiopathic BE Mean age: 52 years 29.7% died Expected death rate 14.7% for males, and 8.9% for females Respiratory causes accounted for 70.4% of deaths Predictors: older age, P. aeruginosa infection, lower FEV1, SGRQ Loebinger et al. Eur Respir J 2009; 34.
Bronchiectasis Severity Index (BSI) Clinical prediction tool for disease severity Derived from a prospective cohort study in the UK - 608 patients Patients with active NTM excluded 9 parameters Validated in several independent cohorts Chalmers et al. AJRCCM 2013; 189.
Bronchiectasis Severity Index Chalmers et al. AJRCCM 2013; 189.
Bronchiectasis Severity Index Independent predictors of hospitalization Prior admissions MRC dyspnea score > 4 FEV 1 < 30% Pseudomonas colonization 3 or more lobes involved on HRCT Chalmers et al. AJRCCM 2013; 189.
Bronchiectasis Severity Index Independent predictors of mortality Older age Low FEV 1 Lower BMI Prior hospitalization 3 or more exacerbations in previous year Chalmers et al. AJRCCM 2013; 189.
FACED Score Classifies severity according to prognosis Derived from an observational study from 7 centers in Spain - 819 patients 5 variables, 7 point score Mild: 0-2 points Moderate: 3-4 points Severe: 5-7 points Martinez-Garcia et al. ERJ 2014.
FACED Score Validated to predict 5-year all-cause mortality Martinez-Garcia et al. ERJ 2014.
E-FACED Score Expanded the capacity of the original tool to predict exacerbations Martinez-Garcia et al. Int J COPD 2017; 12.
Bronchiectasis Mortality: BSI vs FACED Evaluated in a 91 patient cohort followed since 1994 in the UK; median follow-up 18.8 years Both scores were similarly predictive of 5-year and 15-year mortality; FACED did slightly better for the latter Huw et al. ERJ 2016; 47.
Bronchiectasis: Clinical Phenotypes Four clusters identified in European cohort; 3- year follow-up Cluster % of patients Median SGRQ Hospitalizations during 1-yr follow-up Mortality during 1-year follow-up Chronic Pseudomonas Other chronic infection 15.8% 58 42% 5.1% 24.1% 43 16% 1.5% Daily sputum 33.0% 39 16% 3.6% (N=1145) Dry bronchiectasis 27.1% 29 14% 4.9% Aliberti S, et al. Eur Respir J. 2016.
Bronchiectasis: Comorbidities Seitz AE, et al. CHEST 2012; 142.
Bronchiectasis Aetiology Comorbidity Index (BACI) Cohort analysis of 986 outpatients Assesses impact of comorbidities on mortality Median of 4 comorbidities 13 comorbidities independently predicted mortality -> BACI McDonnell et al. Lancet 2016; 4.
Bronchiectasis Aetiology Comorbidity Index (BACI) Predicts 5-year mortality rate, hospitalizations, QOL across all BSI risk strata Validated in 2 independent cohorts: UK and Serbia McDonnell et al. Lancet 2016; 4.
NTM Infection: Impact on QOL Prospective observational study: SGRQ and Medical Outcomes Short-Form (SF-36) 51 patients Mean age 67; 80% were female 84% MAC, 8% M. abscessus 71% had nodular bronchiectatic (NB) pattern, 22% fibrocavitary (FC) 80% actively or previously treated 98% had cough, sputum production, 49% with fatigue, 31% with weight loss Mehta and Marras. Resp Med, 2011
NTM Infection: Impact on QOL Mean SF-36 scores - summary and in all domains - were worse than population-based normals in statistically significant fashion SGRQ also worse than normal No important differences between untreated patients compared to those treated for more than 3 months Multivariate analysis: Higher FVC% and DLCO%: better SF-36 scores Lower FVC% and emphysema: worse SGRQ scores Tendency toward worse SGQR scores for M. abscessus Mehta and Marras. Resp Med, 2011
MAC: Prognostic Factors Retrospective review of 634 HIV negative patients with MAC Mean follow-up period: 4.7 years 76% had NB disease; 16.6%had FC, 4.7% had both Only 27% treated within 6 months 0-1 drug: 479 patients (75.6%) 2-5 drugs: 131 patients (20.7%) Unknown: 24 patients (3.8%) Hayashi al, AJRCCM; 2011, 185.
MAC: Prognostic Factors 160 patients (25.2%) died in follow-up period Overall mortality rates 5-year: 23.9% 10-year: 46.5% MAC-specific mortality rate 5-year: 5.4% 10-year: 15.7% Hayashi al, AJRCCM; 2011, 185.
MAC: Prognostic Factors Negative prognostic factors - all cause mortality Male sex Older age Systemic or respiratory comorbidity Non-nodular bronchiectatic radiographic features BMI < 18.5 kg/m2 Anemia, hypoalbuminemia ESR > 50 Hayashi al, AJRCCM; 2011, 185.
MAC: Prognostic Factors Negative prognostic factors: MAC specific mortality FC or FC + NB radiographic features BMI < 18.5 kg/m2 Anemia CRP > 1 Hayashi al, AJRCCM; 2011, 185.
MAC NB Pattern Retrospective review of 782 HIV negative patients; mean age 68 years Mean follow-up period was 4.3 years Almost 70% of patients did not receive antimicrobial therapy 5 and 10 year mortality All cause: 12.5%, 27.4% Progressive MAC: 2%, 4.8% Radiographic progression: 41.2% Gochi et al, BMJ Open, 2015, 5.
Negative prognostic factors - All cause mortality Male sex Older age BMI < 18.5 kg/m2 Hypoalbuminemia ESR > 40 Absence of bloody sputum Gochi et al, BMJ Open, 2015, 5.
Macrolide Resistant MAC Macrolide monotherapy or combination with a quinolone are risk factors 51 patients, 47%NB, 53% cavitary disease One-year mortality in those who remained culture positive despite therapy was 34% compared to 0% who became culture negative Griffith et al. AJRCCM; 174: 2006
MAC vs Other NTM 167 patients Median survival time: MAC: 13 years Other NTM: 4.6 years Age and serious comorbidities were significant predictors of survival Kotilainen et al. Eur J Clin Microbiol Infect Dis; 2015, 34.
How would you assess the severity of this patient s bronchiectasis? BSI score - 13 FACED score - 5 Both scores - c/w severe bronchiectasis
Summary Natural history and prognosis of bronchiectasis and NTM infection have been difficult to predict A number of validated tools have been developed - BSI, FACED Specific factors associated with worse outcomes Bronchiectasis: Older age, worse lung function, chronic P. aeruginosa infection and comorbidities NTM infection: Older age, male sex, cavitary disease, macrolide resistance